rs144662546
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_006059.4(LAMC3):c.4130C>T(p.Thr1377Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,614,110 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1377T) has been classified as Likely benign.
Frequency
Consequence
NM_006059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.4130C>T | p.Thr1377Ile | missense_variant | 25/28 | ENST00000361069.9 | |
LAMC3 | XM_011518121.2 | c.4148C>T | p.Thr1383Ile | missense_variant | 25/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.4130C>T | p.Thr1377Ile | missense_variant | 25/28 | 2 | NM_006059.4 | P1 | |
LAMC3 | ENST00000355452.5 | c.176C>T | p.Thr59Ile | missense_variant | 3/6 | 1 | |||
LAMC3 | ENST00000678758.1 | c.290C>T | p.Thr97Ile | missense_variant | 3/6 | ||||
LAMC3 | ENST00000678544.1 | n.1703C>T | non_coding_transcript_exon_variant | 3/6 |
Frequencies
GnomAD3 genomes ? AF: 0.00182 AC: 277AN: 152158Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000541 AC: 136AN: 251298Hom.: 0 AF XY: 0.000486 AC XY: 66AN XY: 135884
GnomAD4 exome AF: 0.000193 AC: 282AN: 1461834Hom.: 2 Cov.: 32 AF XY: 0.000179 AC XY: 130AN XY: 727216
GnomAD4 genome ? AF: 0.00181 AC: 276AN: 152276Hom.: 1 Cov.: 33 AF XY: 0.00193 AC XY: 144AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 29, 2015 | - - |
LAMC3-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
See cases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Feb 22, 2020 | ACMG classification criteria: BP1, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at